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Dopamine D2 receptors in discrimination learning and spine enlargement.

Abstract：

:Dopamine D2 receptors (D2Rs) are densely expressed in the striatum and have been linked to neuropsychiatric disorders such as schizophrenia1,2. High-affinity binding of dopamine suggests that D2Rs detect transient reductions in dopamine concentration (the dopamine dip) during punishment learning3-5. However, the nature and cellular basis of D2R-dependent behaviour are unclear. Here we show that tone reward conditioning induces marked stimulus generalization in a manner that depends on dopamine D1 receptors (D1Rs) in the nucleus accumbens (NAc) of mice, and that discrimination learning refines the conditioning using a dopamine dip. In NAc slices, a narrow dopamine dip (as short as 0.4 s) was detected by D2Rs to disinhibit adenosine A2A receptor (A2AR)-mediated enlargement of dendritic spines in D2R-expressing spiny projection neurons (D2-SPNs). Plasticity-related signalling by Ca2+/calmodulin-dependent protein kinase II and A2ARs in the NAc was required for discrimination learning. By contrast, extinction learning did not involve dopamine dips or D2-SPNs. Treatment with methamphetamine, which dysregulates dopamine signalling, impaired discrimination learning and spine enlargement, and these impairments were reversed by a D2R antagonist. Our data show that D2Rs refine the generalized reward learning mediated by D1Rs.

journal_name

Nature

journal_title

Nature

authors

Iino Y,Sawada T,Yamaguchi K,Tajiri M,Ishii S,Kasai H,Yagishita S

doi

10.1038/s41586-020-2115-1

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

555-560

issue

7800

eissn

0028-0836

issn

1476-4687

pii

10.1038/s41586-020-2115-1

journal_volume

579

pub_type

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